tbuckley/cabot-search huggingface dataset:
Nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VRE) ST796, Switzerland, 2017 to 2020
Authors: Vanja Piezzi, Nasstasja Wassilew, Andrew Atkinson, Stéphanie D'Incau, Tanja Kaspar, Helena MB Seth-Smith, Carlo Casanova, Pascal Bittel, Philipp Jent, Rami Sommerstein, Niccolò Buetti, Jonas Marschall
Journal: Eurosurveillance (2022)

A large clonal outbreak caused by vancomycin-resistant Enterococcus faecium (VRE) affected the Bern University Hospital group from the end of December 2017 until July 2020. We describe the characteristics of the outbreak and the bundle of infection prevention and control (IPC) measures implemented. The outbreak was first recognised when two concomitant cases of VRE bloodstream infection were identified on the oncology ward. During 32 months, 518 patients in the 1,300-bed hospital group were identified as vanB VRE carriers. Eighteen (3.5%) patients developed an invasive infection, of whom seven had bacteraemia. In 2018, a subset of 328 isolates were analysed by whole genome sequencing, 312 of which were identified as sequence type (ST) 796. The initial IPC measures were implemented with a focus on the affected wards. However, in June 2018, ST796 caused another increase in cases, and the management strategy was intensified and escalated to a hospital-wide level. The clinical impact of this large nosocomial VRE outbreak with the emergent clone ST796 was modest. A hospital-wide approach with a multimodal IPC bundle was successful against this highly transmissible strain.
A framework for measuring timeliness in the outbreak response path: lessons learned from the Middle East respiratory syndrome (MERS) epidemic, September 2012 to January 2019
Authors: Carolina dos S Ribeiro, Martine van Roode, Elmoubasher Farag, Mohamed Nour, Aya Moustafa, Minahil Ahmed, George Haringhuizen, Marion Koopmans, Linda van de Burgwal
Journal: Eurosurveillance (2022)

Background Epidemics are a constant threat in the 21st century, particularly disease outbreaks following spillover of an animal virus to humans. Timeliness, a key metric in epidemic response, can be examined to identify critical steps and delays in public health action. Aim To examine timeliness, we analysed the response to the Middle East respiratory syndrome (MERS) epidemic, with a focus on the international and One Health response efforts. Methods We performed a historical review of the MERS epidemic between September 2012 and January 2019 in three steps: (i) the construction of a timeline identifying critical events in the global response, (ii) the performance of a critical path analysis to define outbreak milestones and (iii) a time gap analysis to measure timeliness in the execution of these milestones. Results We proposed 14 MERS-specific milestones at different phases of the epidemic, assessing timeliness of the public health response as well as at the animal–human interface, where we identified the most significant delays. Conclusions When comparing timeliness across three coronavirus epidemics, i.e. MERS (2012), SARS (2002) and COVID-19 (2019), we identified clear improvements over time for certain milestones including laboratory confirmation and diagnostics development, while this was not as apparent for others, as the identification of zoonotic hosts. To more efficiently respond to emerging threats, the global health community should widely assess and tackle specific delays in implementing response interventions by addressing challenges in the sharing of information, data and resources, as well as efficiency, quality, transparency and reliability of reporting events.
National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review
Authors: Carlijn C.E. Jordans, Marta Vasylyev, Caroline Rae, Marie Louise Jakobsen, Anna Vassilenko, Nicolas Dauby, Anne Louise Grevsen, Stine Finne Jakobsen, Anne Raahauge, Karen Champenois, Emmanuelle Papot, Jakob J. Malin, T. Sonia Boender, Georg M.N Behrens, Henning Gruell, Anja Neumann, Christoph D. Spinner, Frederik Valbert, Karolina Akinosoglou, Evangelia G. Kostaki, Silvia Nozza, Andrea Giacomelli, Giuseppe Lapadula, Maria Mazzitelli, Carlo Torti, Raimonda Matulionyte, Elzbieta Matulyte, Berend J. Van Welzen, Kathryn S. Hensley, Magdalena Thompson, Magdalena Ankiersztejn-Bartczak, Agata Skrzat-Klapaczyńska, Oana Săndulescu, Adrian Streinu-Cercel, Anca Streinu-Cercel, Viktor Daniel Miron, Anastasia Pokrovskaya, Anna Hachfeld, Antonina Dorokhina, Maryna Sukach, Emily Lord, Ann K. Sullivan, Casper Rokx
Journal: Eurosurveillance (2022)

BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.
Radiopaque Nanorobots as Magnetically Navigable Contrast Agents for Localized In Vivo Imaging of the Gastrointestinal Tract
Authors: Cagatay M. Oral, Martina Ussia, Mario Urso, Jiri Salat, Adam Novobilsky, Michal Stefanik, Daniel Ruzek, Martin Pumera
Journal: Advanced Healthcare Materials (2022)

Magnetic nanorobots offer wireless navigation capability in hard-to-reach areas of the human body for targeted therapy and diagnosis. Though in vivo imaging is required for guidance of the magnetic nanorobots toward the target areas, most of the imaging techniques are inadequate to reveal the potential locomotion routes. This work proposes the use of radiopaque magnetic nanorobots along with microcomputed tomography (microCT) for localized in vivo imaging applications. The nanorobots consist of a contrast agent, barium sulfate (BaSO4 ), magnetized by the decoration of magnetite (Fe3 O4 ) particles. The magnetic features lead to actuation under rotating magnetic fields and enable precise navigation in a microfluidic channel used to simulate confined spaces of the body. In this channel, the intrinsic radiopacity of the nanorobots also provides the possibility to reveal the internal structures by X-ray contrast. Furthermore, in vitro analysis indicates nontoxicity of the nanorobots. In vivo experiments demonstrate localization of the nanorobots in a specific part of the gastrointestinal (GI) tract upon the influence of the magnetic field, indicating the efficient control even in the presence of natural peristaltic movements. The nanorobots reported here highlight that smart nanorobotic contrast agents can improve the current imaging-based diagnosis techniques by providing untethered controllability in vivo.
Using PSMA imaging for prognostication in localized and advanced prostate cancer
Authors: Matthew J. Roberts, Tobias Maurer, Marlon Perera, Matthias Eiber, Thomas A. Hope, Piet Ost, Shankar Siva, Michael S. Hofman, Declan G. Murphy, Louise Emmett, Wolfgang P. Fendler
Journal: Nature Reviews Urology (2022)
Retraction Note: Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease
Authors: Barbara Nuvoli, Sabrina Germoni, Carlotta Morosetti, Raffaela Santoro, Giancarlo Cortese, Serena Masi, Iole Cordone, Rossella Galati
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1476-4598-13-69.
Prognostic significance of <scp>measurable residual disease</scp> in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation in second or later complete remission
Authors: Oren Pasvolsky, Rima M. Saliba, Celina Ledesma, Uday R. Popat, Amin Alousi, Amanda Olson, Betul Oran, Chitra Hosing, Qaiser Bashir, Muzaffar H. Qazilbash, Nicholas J. Short, Farhad Ravandi, Richard Champlin, Elizabeth J. Shpall, Partow Kebriaei
Journal: American Journal of Hematology (2022)
The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium
Authors: Angie Mae Rodday, Susan K. Parsons, Jenica N. Upshaw, Jonathan W. Friedberg, Andrea Gallamini, Eliza Hawkes, David Hodgson, Peter Johnson, Brian K. Link, Eric Mou, Kerry J. Savage, Pier Luigi Zinzani, Matthew Maurer, Andrew M. Evens
Journal: Journal of Clinical Oncology (2022)

The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model.
Sensitive quantitative IgD assay increases progression-free survival prediction accuracy in IgD plasma cell myeloma
Authors: Jin Liu, Jing Lu, Wanting Qiang, Yanchun Jia, Haiyan He, Xiaofei Ye, Wee Joo Chng, Robert Peter Gale, Yang Liang, Jian Hou, Juan Du
Journal: Leukemia (2022)
Excessive proteostasis contributes to pathology in fragile X syndrome
Authors: Susana R. Louros, Sang S. Seo, Beatriz Maio, Cristina Martinez-Gonzalez, Miguel A. Gonzalez-Lozano, Melania Muscas, Nick C. Verity, Jimi C. Wills, Ka Wan Li, Matthew F. Nolan, Emily K. Osterweil
Journal: Neuron (2022)

In fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1-/y) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes. Normalizing proteasome activity with bortezomib corrects excessive hippocampal protein synthesis and hyperactivation of neurons in the inferior colliculus (IC) in response to auditory stimulation. Moreover, systemic administration of bortezomib significantly reduces the incidence and severity of audiogenic seizures (AGS) in the Fmr1-/y mouse, as does genetic reduction of proteasome, specifically in the IC. Together, these results identify excessive activation of the UPS pathway in Fmr1-/y neurons as a contributor to multiple phenotypes that can be targeted for therapeutic intervention.
Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial
Authors: Sara A Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Wing Yan Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, José Manuel Perez-Garcia, Sung-Bae Kim, Vanessa Petry, Chiun-Sheng Huang, Wei Li, Jean-Sebastien Frenel, Silvia Antolin, Winnie Yeo, Giampaolo Bianchini, Sherene Loi, Junji Tsurutani, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortés
Journal: The Lancet (2022)
Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis
Authors: Lixiang Zhai, Chunhua Huang, Ziwan Ning, Yijing Zhang, Min Zhuang, Wei Yang, Xiaolei Wang, Jingjing Wang, Lu Zhang, Haitao Xiao, Ling Zhao, Pallavi Asthana, Yan Y. Lam, Chi Fung Willis Chow, Jian-dong Huang, Shuofeng Yuan, Kui Ming Chan, Chun-Su Yuan, Johnson Yiu-Nam Lau, Hoi Leong Xavier Wong, Zhao-xiang Bian
Journal: Cell Host & Microbe (2022)
Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases
Authors: Wai Hon Chooi, Chong Yi Ng, Valerie Ow, Jasmine Harley, Winanto Ng, Jin‐Hui Hor, Kay En Low, Benoit Malleret, Kun Xue, Shi‐Yan Ng
Journal: Advanced Healthcare Materials (2022)

In the process of generating organoids, basement membrane extracts or Matrigel are often used to encapsulate cells but they are poorly defined and contribute to reproducibility issues. While defined hydrogels are increasingly used for organoid culture, the effects of replacing Matrigel with a defined hydrogel on neural progenitor growth, neural differentiation, and maturation within organoids are not well-explored. In this study, the use of alginate hydrogels as a Matrigel substitute in spinal cord organoid generation is explored. It is found that alginate encapsulation reduces organoid size variability by preventing organoid aggregation. Importantly, alginate supports neurogenesis and gliogenesis of the spinal cord organoids at a similar efficiency to Matrigel, with mature myelinated neurons observed by day 120. Furthermore, using alginate leads to lower expression of non-spinal markers such as FOXA2, suggesting better control over neural fate specification. To demonstrate the feasibility of using alginate-based organoid cultures as disease models, an isogenic pair of induced pluripotent stem cells discordant for the ALS-causing mutation TDP43G298S is used, where increased TDP43 mislocalization in the mutant organoids is observed. This study shows that alginate is an ideal substitute for Matrigel for spinal cord organoid derivation, especially when a xeno-free and fully defined 3D culture condition is desired.
Hamstring injury rates have increased during recent seasons and now constitute 24% of all injuries in men’s professional football: the UEFA Elite Club Injury Study from 2001/02 to 2021/22
Authors: Jan Ekstrand, Håkan Bengtsson, Markus Waldén, Michael Davison, Karim M Khan, Martin Hägglund
Journal: British Journal of Sports Medicine (2022)

Objectives To: (1) describe hamstring injury incidence and burden in male professional football players over 21 seasons (2001/02 to 2021/22); (2) analyse the time-trends of hamstring muscle injuries over the most recent eight seasons (2014/15 to 2021/22); and (3) describe hamstring injury location, mechanism and recurrence rate. Methods 3909 players from 54 teams (in 20 European countries) from 2001/02 to 2021/22 (21 consecutive seasons) were included. Team medical staff recorded individual player exposure and time-loss injuries. Time-trend analyses were performed with Poisson regression using generalised linear models. Results 2636 hamstring injuries represented 19% of all reported injuries, with the proportion of all injuries increasing from 12% during the first season to 24% in the most recent season. During that same period, the percentage of all injury absence days caused by hamstring injuries increased from 10% to 20%. Between 2014/15 and 2021/22, training hamstring injury incidence increased (6.7% annually, 95% CI 1.7% to 12.5%) as did burden (9.0% annually, 95% CI 1.2% to 18.3%). During those years, the match hamstring injury incidence also increased (3.9% annually, 95% CI 0.1% to 7.9%) and with the same trend (not statistically significant) for match hamstring injury burden (6.2% annually, 95% CI −0.5% to 15.0%). Conclusions Hamstring injury proportions—in number of injuries and total absence days—doubled during the 21-year period of study. During the last eight seasons, hamstring injury rates have increased both in training and match play.
Nanomedicine‐boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma
Authors: Yi Lu, Yue Gao, Huan Yang, Yong Hu, Xin Li
Journal: Military Medical Research (2022)

Traditional treatments for advanced hepatocellular carcinoma (HCC), such as surgical resection, transplantation, radiofrequency ablation, and chemotherapy are unsatisfactory, and therefore the exploration of powerful therapeutic strategies is urgently needed. Immunotherapy has emerged as a promising strategy for advanced HCC treatment due to its minimal side effects and long-lasting therapeutic memory effects. Recent studies have demonstrated that icaritin could serve as an immunomodulator for effective immunotherapy of advanced HCC. Encouragingly, in 2022, icaritin soft capsules were approved by the National Medical Products Administration (NMPA) of China for the immunotherapy of advanced HCC. However, the therapeutic efficacy of icaritin in clinical practice is impaired by its poor bioavailability and unfavorable in vivo delivery efficiency. Recently, functionalized drug delivery systems including stimuli-responsive nanocarriers, cell membrane-coated nanocarriers, and living cell-nanocarrier systems have been designed to overcome the shortcomings of drugs, including the low bioavailability and limited delivery efficiency as well as side effects. Taken together, the development of icaritin-based nanomedicines is expected to further improve the immunotherapy of advanced HCC. Herein, we compared the different preparation methods for icaritin, interpreted the HCC immune microenvironment and the mechanisms underlying icaritin for treatment of advanced HCC, and discussed both the design of icaritin-based nanomedicines with high icaritin loading and the latest progress in icaritin-based nanomedicines for advanced HCC immunotherapy. Finally, the prospects to promote further clinical translation of icaritin-based nanomedicines for the immunotherapy of advanced HCC were proposed.
Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
Authors: Celeste Rizzello, Valeria Cancila, Sabina Sangaletti, Laura Botti, Chiara Ratti, Matteo Milani, Matteo Dugo, Francesco Bertoni, Claudio Tripodo, Claudia Chiodoni, Mario P. Colombo
Journal: Molecular Cancer (2022)

Abstract Background Autoimmune disorders, including Systemic Lupus Erythematosus (SLE), are associated with increased incidence of hematological malignancies. The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. Although widely studied for its pro-tumorigenic role in different solid tumours, the role of OPN in autoimmunity-driven lymphomagenesis has not been investigated yet. Methods To test the role of OPN in the SLE-associated lymphomagenesis, the SLE-like prone Fas lpr/lpr mutation was transferred onto an OPN-deficient background. Spleen from Fas lpr/lpr and OPN-/-Fas lpr/lpr mice, as well as purified B cells, were analysed by histopathology, flow cytometry, Western Blot, immunohistochemistry, immunofluorescence and gene expression profile to define lymphoma characteristics and investigate the molecular mechanisms behind the observed phenotype. OPN cellular localization in primary splenic B cells and mouse and human DLBCL cell lines was assessed by confocal microscopy. Finally, gain of function experiments, by stable over-expression of the secreted (sOPN) and intracellular OPN (iOPN) in OPN-/-Fas lpr/lpr -derived DLBCL cell lines, were performed for further validation experiments. Results Despite reduced autoimmunity signs, OPN-/-Fas lpr/lpr mice developed splenic lymphomas with higher incidence than Fas lpr/lpr counterparts. In situ and ex vivo analysis featured such tumours as activated type of diffuse large B cell lymphoma (ABC-DLBCL), expressing BCL2 and c-MYC, but not BCL6, with activated STAT3 signaling. OPN-/-Fas lpr/lpr B lymphocytes showed an enhanced TLR9-MYD88 signaling pathway, either at baseline or after stimulation with CpG oligonucleotides, which mimic dsDNA circulating in autoimmune conditions. B cells from Fas lpr/lpr mice were found to express the intracellular form of OPN. Accordingly, gene transfer-mediated re-expression of iOPN, but not of its secreted isoform, into ABC-DLBCL cell lines established from OPN-/-Fas lpr/lpr mice, prevented CpG-mediated activation of STAT3, suggesting that the intracellular form of OPN may represent a brake to TLR9 signaling pathway activation. Conclusion These data indicate that, in the setting of SLE-like syndrome in which double strand-DNA chronically circulates and activates TLRs, B cell intracellular OPN exerts a protective role in autoimmunity-driven DLBCL development, mainly acting as a brake in the TLR9-MYD88-STAT3 signaling pathway.
Stool multi-omics for the study of host–microbe interactions in inflammatory bowel disease
Authors: Consuelo Sauceda, Charlie Bayne, Khadijeh Sudqi, Antonio Gonzalez, Parambir S. Dulai, Rob Knight, David J. Gonzalez, Carlos G. Gonzalez
Journal: Gut Microbes (2022)

Inflammatory Bowel Disease (IBD) is a chronic immune-mediated inflammatory disease of the gastrointestinal tract that is a growing public burden. Gut microbes and their interactions with hosts play a crucial role in disease pathogenesis and progression. These interactions are complex, spanning multiple physiological systems and data types, making comprehensive disease assessment difficult, and often overwhelming single-omic capabilities. Stool-based multi-omics is a promising approach for characterizing host-gut microbiome interactions using deep integration of technologies such as 16S rRNA sequencing, shotgun metagenomics, meta-transcriptomics, metabolomics, and metaproteomics. The wealth of information generated through multi-omic studies is poised to usher in advancements in IBD research and precision medicine. This review highlights historical and recent findings from stool-based muti-omic studies that have contributed to unraveling IBD's complexity. Finally, we discuss common pitfalls, issues, and limitations, and how future pipelines should address them to standardize multi-omics in IBD research and beyond.
From intestinal colonization to systemic infections: <i>Candida albicans</i> translocation and dissemination
Authors: Jakob L. Sprague, Lydia Kasper, Bernhard Hube
Journal: Gut Microbes (2022)

Candida species are the most prevalent cause of invasive fungal infections, of which Candida albicans is the most common. Translocation across the epithelial barrier into the bloodstream by intestinal-colonizing C. albicans cells serves as the main source for systemic infections. Understanding the fungal mechanisms behind this process will give valuable insights on how to prevent such infections and keep C. albicans in the commensal state in patients with predisposing conditions. This review will focus on recent developments in characterizing fungal translocation mechanisms, compare what we know about enteric bacterial pathogens with C. albicans, and discuss the different proposed hypotheses for how C. albicans enters and disseminates through the bloodstream immediately following translocation.